鱼腥草素钠对氧化镍纳米颗粒诱导大鼠肺部氧化应激损伤的保护作用OA

[Background]Nickel oxide nanoparticles(NiO NPs)are widely used in industrial applications and can enter the body through the respiratory tract,where they may induce oxidative stress,in-flammation,and lung tissue injury,posing a substantial occupational and environmental health risk.Sodium houttuyfonate(SH)exhibits anti-inflammatory,antioxidant,and immunomodulatory properties,alongside a favorable safety profile. [Objective]To investigate the protective effects of SH against NiO NP-induced oxidative stress and injury,and to explore the possible molecular mechanisms involved. [Methods]Both in vitro and in vivo experiments were conducted to establish NiO NP-induced lung injury models and to evaluate the effects of SH and its different formulations on oxidative stress injury.In the in vitro experiment,a NiO NP-induced injury model was established in rat alveolar type II epithelial cells(ACE-II).Malondialdehyde(MDA)levels,glutathione(GSH)levels,and superoxide dismutase(SOD)activity were measured.The gene and protein expression levels of molecules in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Keap1-Nrf2/HO-1)signaling pathway were detected by quantitative real-time PCR(qPCR)and Western blotting.In the in vivo experiment,a NiO NP exposure model was established in Wistar rats.SH and its formulations were administered by gavage or aerosol inhalation,and the above oxidative stress and signaling pathway indicators were examined in lung tissue. [Results]After NiO NP exposure,GSH levels and SOD activity in ACE-II cells were significantly decreased,while MDA levels were significantly increased(P<0.001,P<0.01,and P<0.001,respectively).SH intervention increased GSH levels and SOD activity and reduced MDA levels(P<0.05).NiO NPs also upregulated the mRNA and protein expression of Keap1 and downregulated the mRNA and protein expression of Nrf2 and HO-1(P<0.05),while SH treatment reversed these changes to varying degrees.In the in vivo experiment,GSH levels and SOD activity in lung tissue were decreased,whereas MDA levels were increased in the model group(P<0.05).Histopathological examination showed thickening of the alveolar wall,inflammatory cell infiltration,and focal congestion and hemorrhage.All SH formulations increased GSH levels and SOD activity and alleviated pathological lung injury.Among the tested formulations,the nanoemulsion aerosol group showed a more pronounced regulatory effect on molecules related to the Keap1-Nrf2/HO-1 pathway(P<0.05). [Conclusion]SH significantly alleviates NiO NP-induced pulmonary oxidative stress injury by reducing MDA levels,enhancing GSH levels and SOD activity,and modulating the Keap1-Nrf2/HO-1 signaling pathway.These findings suggest that SH has antioxidant protective po-tential against NiO NP-induced lung injury.The nanoemulsion aerosol formulation may enhance the bioavailability of SH,providing ex-perimental evidence for developing pharmacological strategy against NiO NP-induced pulmonary injury.